Many potent analogs of LHRH (the luteinizing hormone releasing hormone, pGlu.sup.1, His.sup.2, Trp.sup.3, Ser.sup.4, Tyr.sup.5, Gly.sup.6, Leu.sup.7, Arg.sup.8, Pro.sup.9, Gly.sup.10 - NH.sub.2) have structural features which cause release of histamine from mast cells (Karten et al., 1986). These features include a group of hydrophobic amino acids at the N-terminal and strongly basic residues in positions 6 and 8, notably D-Arg.sup.6, Arg.sup.8. A prime example of this class of analogs is (N-Ac-D-2-Na1.sup.1, D-4F-Phe.sup.2 D-Trp.sup.3, D-Arg.sup.6)- LHRH (Schmidt et al.). Some analogs bind to rat peritoneal mast cells and membrane preparations and that the binding was related to the release of histamine (Sundaram et al.). For a recent review of LHRH analogs, see Janecka, et al. (1994).
Abbreviations for the unnatural amino acids mentioned herein are included in the following list:
______________________________________ AABLys N.sup..epsilon. -(4-acetylaminobenzoyl)lysine AALys N.sup..epsilon. -anisinoyl-lysine AAPhe 3-(4-acetylaminophenyl)lysine Abu 2-aminobutyric acid ACLys N.sup..epsilon. -(6-aminocaproyl)lysine ACyh 1-aminocyclohexanecarboxylic acid ACyp 1-aminocyclopentanecarboxylic acid Aile alloisoleucine Ala alanine AnGlu 4-(4-methoxy-phenylcarbamoyl)-2-aminobutyric acid 2ANic 2-aminonicotinic acid 6ANic 6-aminonicotinic acid APic 6-aminopicolinic acid APh 4-aminobenzoic acid APhe 4-aminophenylalanine APz 3-amino-2-pyrazinecarboxylic acid Aze azetidine-2-carboxylic acid Bim 5-benzimidazolecarboxylic acid BzLys N.sup..epsilon. -benzoyllysine Cit citrulline Cl.sub.2 Phe 3-(3,4-dichlorophenyl)alanine Cpa 3-(4-chlorophenyl)alanine cPzACAla cis-3-(4- pyrazinylcarbonylaminocyclohexyl)alanine cPmACAla cis-3-(4-(4- pyrimidylcarbonyl)aminocyclohexyl)alanine Dbf 3-(2-dibenzofuranyl)alanine DMGLys N.sup..epsilon. -(N,N-dimethylglycyl)lysine Dpo N.sup..epsilon. -(4,6-dimethyl-1-pyrimidyl)-ornithine F.sub.2 Ala 3,3-difluoroalanine hNal 4-(2-naphthyl)-2-aminobutyric acid HOBLys N.sup..epsilon. -=(4-hydroxybenzoyl)lysine hpClPhe 4-(4-chlorophenyl)-2-amino-butyric acid Hse homoserine (2-amino-4-hydroxybutanoic acid) ICapLys N.sup..epsilon. -(6-isopropylaminocaproyl)lysine ILys N.sup..epsilon. -isopropyllysine Ind indoline-2-carboxylic acid INicLys N.sup..epsilon. -isonicotincyllysine IOrn N.sup..delta. -isopropylornithine Me.sub.3 Arg N.sup.G,N.sup.G,N.sup.G -trimethylarginine Me.sub.2 Lys N.sup..epsilon., N.sup..epsilon. -dimethyllysine MNal 3-((6-methyl)2-naphtyl)alanine MNicLys N.sup..epsilon. -(6-methylpicolinoyl)lysine MOB 4-methoxybenzoyl MpClPhe N-methyl-3-(4-chlorophenyl)lysine MPZGlu glutamic acid, y-4-methylpiperazine NAcDNal N-acetyl-3-12-naphthyl)alanine NacDQal N-acetyl-3-(3-quinolyl)alanine Nal 3-(2-naphthyl)alanine Nap 2-naphthoic acid NapDThr N-naphthoyl-D-threonine NicLys N.sup..epsilon. -nicotinoyllysine NO.sub.2 B 4-nitrobenzoyl NO.sub.2 Phe 3-(4-nitrophenyl)alanine oClPhe 3-(2-chlorophenyl)alanine Opt O-phenyl-tyrosine Orn ornithine Pal 3-(3-pyridyl)alanine 21Pal 3-(2-pyridyl)alanine 2PALys N.sup..epsilon. -(3-pyridylacetyl)lysine pCapLys N.sup..epsilon. -(5-picolinoylaminocaproyl)lysine pClPhe 3-(4-chlorophenyl)alanine pFPhe 3-(4-fluorophenyl)-alanine Pic picolinic acid PicLys N.sup..epsilon. -picolinoyllysine PicSar N-picolinoylsarcosinyl Pip piperidine-2-carboxylic acid PmcLys N.sup..epsilon. --(4-pyrimidylcarbonyl)lysine Ptf 3-(4-trifluoromethyl) phenylalanine Pz pyrazinecarboxylic acid PzAla 3-pyrazinylalanine PzAPhe 3-(4-pyrazinylcarbonylaminophenyl)alanine Qal 3-(3-quinolyl)alanine Qnd-Lys N.sup..epsilon. -quinaldoyllysine Qui 3-quinolinecarboxylic acid Qux 2-quinoxalinecarboxylic acid Tic 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid TinGly 2-thienylglycine tNACAla trans-3-(4-nicotinoylaminocyclohexyl)-alanine tPACAla trans-3-(4-picolinoylaminocyclohexyl)alanine ______________________________________